High-affinity interaction between gram-negative flagellin and a cell surface polypeptide results in human monocyte activation.

Flagella from diverse gram-negative bacteria induce tumor necrosis factor alpha (TNF-alpha) and interleukin-1beta (IL-1beta) synthesis by human monocytes (F. Ciacci-Woolwine, P. F.

Induction of cytokine synthesis by flagella from gram-negative bacteria may be dependent on the activation or differentiation state of human monocytes.

We have previously demonstrated that salmonellae, but not Escherichia coli or Yersinia enterocolitica, stimulates tumor necrosis factor alpha (TNFalpha) production in the human promonocytic cell line U38. Subsequent analysis revealed that the TNFalpha-inducing activity of salmonellae was associated with flagellin, a major component of flagella from gram-negative bacteria. In the present study, we have explored the basis for the apparent specificity of action of Salmonella flagella on TNFalpha expression in U38 cells and have extended this analysis to normal human peripheral blood mononuclear cells (PBMC).

Salmonella flagellin induces tumor necrosis factor alpha in a human promonocytic cell line.

During infection of the gastrointestinal tract, salmonellae induce cytokine production and inflammatory responses which are believed to mediate tissue damage in the host. In a previous study, we reported that salmonellae possess the ability to stimulate tumor necrosis factor alpha (TNF-alpha) accumulation in primary human monocytes, as well as in the human promonocytic cell line U38. In this model system, cytokine upregulation is not due to lipopolysaccharide but is mediated by a released protein.

Salmonellae activate tumor necrosis factor alpha production in a human promonocytic cell line via a released polypeptide.

Invasive strains of Salmonella spp. cause both systemic and localized infections in humans. The ability to resist infection and some aspects of the tissue pathology associated with the presence of Salmonella in the gastrointestinal tract have been shown to be mediated in part by the induction of tumor necrosis factor alpha (TNF-alpha), a proinflammatory cytokine produced by activated macrophages and lymphocytes.